林奇综合征相关卵巢癌新进展

林奇综合征（Lynch syndrome,LS）是一种常染色体显性肿瘤综合征,是由DNA错配修复（MMR）基因中的一个胚系突变使细胞具有高微卫星不稳定表型（MSI-H）的超突变或缺乏MMR蛋白表达从而引起肿瘤的发生。突变携带者具有罹患结直肠癌、子宫内膜癌和卵巢癌等一系列恶性肿瘤的高风险。虽然LS中最常见的是结直肠癌,但约有60％的LS首发癌为妇科恶性肿瘤（如子宫内膜癌、卵巢癌等）,且其被诊断年龄较早、组织病理学大多为子宫内膜样或非浆液性类型、总体存活率良好。因此及时发现LS相关卵巢癌（LSAOC）这一亚类,对于预防LS患者其他肿瘤的发生,提高LS患者的生存率具有重要意义。目前关于LS的发病机制、组织病理学等方面不断有新的探索,现就LSAOC的早期诊断、组织病理学、筛查及降低风险方案的最新进展进行综述。     

遗传性妇科肿瘤致病基因携带者的肿瘤筛查

<正>卵巢癌、子宫内膜癌、子宫颈癌是最常见的女性三大恶性肿瘤。遗传性乳腺癌-卵巢癌综合征(hereditary breast and ovarian cancer syndromes, HBOCS)、林奇综合征(Lynch syndromes, LS)、Cowden综合征和黑斑息肉综合征(Peutz-Jeghers syndromes, PJS)与遗传性卵巢癌、子宫内膜癌、子宫颈癌相关。据统计，     

妇科恶性肿瘤血清及腹水层粘蛋白测定及临床意义

目的测定子宫内膜癌及卵巢癌患者血清层粘蛋白(1aminin,LN)含量及切除肿瘤对其影响.方法用放射免疫法测定14例子宫内膜癌,2例子宫内膜增殖症,8例卵巢癌,76例妇科良性疾病患者术前及部分内膜癌和卵巢癌术后血清LN含量,还测定了4例卵巢癌腹水中的含量.结果子宫内膜癌患者血清LN明显高于子宫内膜增殖症及其他各良性疾病组(P＜0.05)且与肌层浸润程度有关,卵巢癌血清LN也明显高于各良性疾病组但统计学分析无差异,其腹水LN明显高于血清(P＜0.05);手术切除肿瘤后,两种恶性肿瘤血清LN水平均显著下降(P＜0.05).结论血清及腹水LN水平与肿瘤的浸润过程密切相关;观察其变化对子宫内膜癌及卵巢癌的诊断、病情判断及监测可能有一定参考价值.     

林奇综合征与妇科肿瘤

林奇综合征（Lynch syndrome）又称为遗传性非息肉性结直肠癌综合征（HNPCC）,属于常染色体显性遗传性疾病,是最常见的结直肠癌遗传形式。林奇综合征患者常会患有多种肿瘤,其中子宫内膜癌及卵巢癌与其关系最为密切,可以视为林奇综合征的“前哨”肿瘤。在诊断患有林奇综合征的女性中,其患子宫内膜癌的终生风险（60%）会高于患结直肠癌的风险。结合临床表现标准及肿瘤分子学评估可以对其进行高效的诊断。在林奇综合征的女性患者中,应每1～2年（而不是每年）进行子宫内膜活检,在生育结束后行预防性手术可以起到有效的筛查及预防作用。对林奇综合征及其相关的子宫内膜癌及卵巢癌不断有新的研究进展,主要对林奇综合征的诊断、相关的子宫内膜癌及卵巢癌进行综述。     

p27蛋白在子宫内膜癌组织中的表达及其临床意义

目的 :探讨p2 7在子宫内膜癌组织中的表达及其临床意义。方法 :采用免疫组化S -P法测定 16份正常子宫内膜、18份子宫内膜不典型增生及 50份子宫内膜癌组织中的p2 7蛋白表达。结果 :p2 7蛋白在子宫内膜癌、子宫内膜不典型增生及正常子宫内膜中的表达率分别为 34%、6 6 .6 7%和 93.75% ,正常子宫内膜及不典型增生组均显著高于子宫内膜癌组 ,差异有显著性 (P <0 .0 5)。p2 7蛋白表达与子宫内膜癌组织学分级、肌层浸润程度及患者预后显著相关 (P <0 .0 5) ,但与临床分期无关。结论 :p2 7蛋白表达下降或缺失可能在子宫内膜癌的发生、发展中起重要作用 ,并可能提示患者的预后     

机器人手术在妇科恶性肿瘤手术治疗中的应用

机器人技术的出现使外科微创手术进入新的发展阶段.在妇科恶性肿瘤手术治疗中机器人也逐步得到应用,其主要应用于宫颈癌的广泛性全子宫切除和盆腔淋巴清扫术,此外机器人根治性宫颈切除术、晚期宫颈癌分期手术及复发性宫颈癌的盆腔脏器切除术也有相关报道;子宫内膜癌和卵巢癌的机器人分期手术也日趋增多.目前,机器人手术多是回顾性病例报告,...     

Lynch综合征相关妇科肿瘤的临床思考

Lynch综合征(lynch syndrome,LS),又称遗传性非息肉状结直肠癌(hereditary non-polyposis colorectal cancer,HNPCC),属常染色体显性遗传性疾病,由DNA错配修复(mismatch repair,MMR)基因突变引起,其发病率约占结直肠癌的2％ ～5％[1-2].根据有无肠外肿瘤将LS分为Ⅰ型和Ⅱ型:Ⅰ型仅表现为结直肠癌;Ⅱ型除结直肠癌外,还表现为多样性肠外肿瘤,常见的有子宫内膜癌和卵巢癌.某些Ⅱ型LS患者家族中还发生其他恶性肿瘤,如胃癌、小肠癌、胰腺癌、甲状腺癌、尿道癌、脑肿瘤、皮肤癌等.近年,越来越多的证据显示,女性LS患者一生中发生子宫内膜癌(内膜癌)的风险为40％～60％,已超过结直肠癌(49％).更有意义的是,高达68％的LS患者首发恶性肿瘤为内膜癌.     

钙通道TRPV6基因在子宫内膜癌表达及其临床意义的初步研究

目的:研究TRPV6在子宫内膜癌组织的表达及其与临床病理特征的关系。方法:选取58例子宫内膜癌石蜡切片,用免疫组化法测定TRPV6的分布及表达,分析其与临床病理之间的关系;另取31例正常子宫内膜及13例不典型增生内膜石蜡切片为对照。选取15例子宫内膜腺癌及11例正常子宫内膜新鲜组织标本,以实时定量PCR方法检测TRPV6的表达。结果:(1)TRPV6在子宫内膜癌组织的表达主要位于胞膜及胞浆内,阳性表达率77.6%,显著低于非绝经期子宫内膜组织(100%)及不典型增生子宫内膜组织(100%)(P0.05),且前者表达强度显著低于后二者(P0.01)。mRNA水平研究表明TRPV6在内膜癌组织中的表达也显著低于正常内膜组织(P0.05);(2)绝经后子宫内膜癌患者TRPV6阳性表达率为71.8%,显著低于未绝经患者(89.5%);(3)在子宫内膜癌组织中,宫颈受累者TRPV6阳性率显著高于宫颈未受累者(89.3%vs 67.7%,P=0.039)。结论:TRPV6在子宫内膜癌组织的表达低于正常子宫内膜组织,TRPV6阳性表达者较多发生子宫内膜癌宫颈受侵,表明钙通道蛋白TRPV6与子宫内膜癌有一定的关系,为探讨子宫内膜癌发病分子机制提供了研究资料。     

促性腺激素释放激素类似物在妇科恶性肿瘤中的应用

根据作用机制不同,促性腺激素释放激素类似物(GnRH-A)可分为两类:激动剂和拮抗剂。研究证实,约80%的卵巢癌以及子宫内膜癌能够表达GnRH及其受体,GnRH-A通过间接抑制下丘脑-垂体-性腺轴或通过自分泌及旁分泌直接抑制肿瘤细胞的增殖。GnRH-A曾被用于治疗晚期或复发的子宫内膜癌和卵巢癌,但疗效不明显。而目前研究的热点是将GnRH-A用于保留早期子宫内膜癌患者的生育功能以及保护肿瘤化疗患者的卵巢功能。GnRH-A还可用于妇科恶性肿瘤的靶向治疗。     

雌激素膜受体GPR30在子宫内膜癌的表达及意义

目的:探讨雌激素膜受体GPR30在子宫内膜癌的表达及意义。方法:RT-PCR和免疫组织化学法检测子宫内膜癌组织和正常子宫内膜组织中GPR30mRNA和蛋白的表达,分析GPR30表达与临床病理的联系;免疫细胞化学分析GPR30蛋白在子宫内膜癌细胞系RL95-2(ER+)和KLE(ER-)的表达。结果:子宫内膜癌组织GPR30mRNA的表达水平显著高于正常子宫内膜组织(P<0.05);子宫内膜癌组织GPR30蛋白表达阳性率(21/30,70%)显著高于正常子宫内膜组织(5/17,29.41%)(χ2=7.232,P=0.007);肿瘤组织学分级越高,GPR30表达阳性率越高(P=0.003),GPR30表达与内膜癌分期、肌层浸润深度和腹水转移无关(P>0.05);ERα阳性的子宫内膜癌细胞系RL95-2和ERα阴性的细胞系KLE均表达GPR30。结论:雌激素膜受体GPR30于子宫内膜癌组织和子宫内膜癌细胞系均有表达,与肿瘤组织学高分级相关,提示GPR30可能在子宫内膜癌中发挥重要的作用。     

Hereditary Endometrial Cancer: Lynch Syndrome

Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), Cowden syndrome (CS), and Peutz-Jeghers syndrome (PJS) are hereditary diseases with an increased risk for endometrial cancer. Lynch syndrome is the most frequent disease associated with hereditary endometrial cancer. Lynch syndrome is autosomal dominant disorder caused by germ-cell mutation of DNA mismatch repair genes. Patients with Lynch syndrome have a higher risk of endometrial cancer compared with the general population. Thus, these patients and their families may develop malignant tumors, including colon and endometrial cancers. The lifetime risk of endometrial cancer in females with Lynch syndrome is particularly high (28-60 %). Lynch syndrome is a typical hereditary tumor associated with endometrial cancer, and elucidation of the oncogenic mechanism is important to understand the characteristics of endometrial cancer, including sporadic endometrial cancer. The Amsterdam II Criteria are used for screening for Lynch syndrome, but some cases of hereditary endometrial cancer do not meet these criteria (masked Lynch syndrome); therefore, patients with a suspected hereditary predisposition, including juvenile-onset and double cancer, should undergo genetic tests in addition to taking of a family history.     

Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast/Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk ovarian cancer. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2 or MSH6, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancer as well as a 9-12% lifetime risk of ovarian cancer. Genetic risk assessment enables physicians to provide individualized evaluation of the likelihood of having one of these gynecologic cancer predisposition syndromes, as well the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Hereditary cancer risk assessment is a process that includes assessment of risk, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from hereditary cancer risk assessment for Hereditary Breast/Ovarian Cancer and the Lynch/Hereditary Non-Polyposis Colorectal Cancer syndrome.     

Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families

OBJECTIVE: Women from Lynch syndrome/hereditary nonpolyposis colorectal cancer (Lynch/HNPCC) families have an increased lifetime risk of developing endometrial and ovarian cancer. This study models a comparison of management strategies for women who carry a Lynch/HNPCC mutation. METHODS: A decision analytic model with three arms was designed to compare annual gynecologic examinations with annual screening (ultrasonography, endometrial biopsy, CA 125) and with hysterectomy with bilateral salpingo-oophorectomy at age 30 years The existing literature was searched for studies on the accuracy of endometrial and ovarian cancer screening using endometrial biopsy, transvaginal ultrasonography, and serum CA 125. The Surveillance, Epidemiology and End Results database from 1988 to 2001 was used to estimate cancer mortality outcomes. RESULTS: In the surgical arm, 0.0056% of women were diagnosed with ovarian cancer and 0.0060% of women with endometrial cancer. These numbers increased to 3.7% and 18.4% in women being screened, and 8.3% and 48.7% in women undergoing annual examinations, respectively. Surgical management led to the longest expected survival time at 79.98 years, followed by screening at 79.31 years, and annual examinations at 77.41 years. If starting at age 30 and discounting life years at 3%, surgery still leads to the greatest expected life years. When comparing prophylactic surgery with the screening option, one would need to perform 75 surgeries to save one woman's entire life. For cancer prevention, however, only 28 and 6 prophylactic surgeries would need to be performed to prevent one case of ovarian and endometrial cancer, respectively. CONCLUSION: Risk-reducing hysterectomy and bilateral salpingo-oophorectomy may be considered in women with Lynch/HNPCC to prevent gynecologic cancers and their associated morbidities.     

Screening and diagnosis of endometrial cancer in Lynch syndrome

Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition syndrome caused by a mismatch of DNA repair (MMR system). Lifetime risk of developing endometrial and ovarian cancer in LS is higher than in the general population and gynecologic screening appears interesting. Screening is based on several tests: pelvic ultrasound, endometrial biopsy and hysteroscopy for endometrial cancer, pelvic ultrasound and CA125 for ovarian cancer. Those tests appear efficient for the diagnosis of gynecologic cancers in LS. Nevertheless, screening tests have not proved clinical benefit until now, and potential problems of compliance, risk of false negative cases, and interval cancer associated with screening do justify offering prophylactic surgery to patients. Women with LS should be informed of the potential benefits and risks of screening and the importance of evaluation in case of gynecologic symptoms or abnormal bleeding. Chemoprevention by progestin-containing oral contraceptives and the treatment of premalignant lesion are available options for reducing the risk of endometrial cancer in LS population.     

Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis colorectal cancer syndrome

OBJECTIVE: Women with hereditary nonpolyposis colorectal cancer syndrome have a 40-60% lifetime risk for colon cancer, a 40-60% lifetime risk for endometrial cancer, and a 12% lifetime risk for ovarian cancer. A number of women with hereditary nonpolyposis colorectal cancer syndrome will have more than one cancer in their lifetime. The purpose of this study was to estimate whether women with hereditary nonpolyposis colorectal cancer syndrome who develop 2 primary cancers present with gynecologic or colon cancer as their "sentinel cancer." METHODS: Women whose families fulfilled Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome and who developed 2 primary colorectal/gynecologic cancers in their lifetime were identified from 5 large hereditary nonpolyposis colorectal cancer syndrome registries. Information on age at cancer diagnoses and which cancer (colon cancer or endometrial cancer/ovarian cancer) developed first was obtained. RESULTS: A total of 117 women with dual primary cancers from 223 Amsterdam families were identified. In 16 women, colon cancer and endometrial cancer/ovarian cancer were diagnosed simultaneously. Of the remaining 101 women, 52 (51%) women had an endometrial or ovarian cancer diagnosed first. Forty-nine (49%) women had a colon cancer diagnosed first. For women who developed endometrial cancer/ovarian cancer first, mean age at diagnosis of endometrial cancer/ovarian cancer was 44. For women who developed colon cancer first, the mean age at diagnosis of colon cancer was 40. CONCLUSION: In this large series of women with hereditary nonpolyposis colorectal cancer syndrome who developed 2 primary colorectal/gynecologic cancers, endometrial cancer/ovarian cancer was the "sentinel cancer," preceding the development of colon cancer, in half of the cases. Therefore, gynecologists and gynecologic oncologists play a pivotal role in the identification of women with hereditary nonpolyposis colorectal cancer syndrome.     

Synchronous occult cancers of the endometrium and fallopian tube in an MSH2 mutation carrier at time of prophylactic surgery

BackgroundWomen with Lynch syndrome have a 40 to 60% lifetime risk of endometrial cancer and a 10 to 12% lifetime risk of ovarian cancer and may consider prophylactic gynecological surgery as an option for risk reduction.CaseWe report a case of synchronous primary cancers of the endometrium and fallopian tube diagnosed at time of prophylactic surgery in an MSH2 mutation carrier.ConclusionRisk-reducing gynecological surgery in Lynch syndrome must include complete removal of the fallopian tubes in addition to the ovaries and endometrium, followed by careful pathological review. Prospective studies are needed to clarify the incidence of occult primary carcinoma of the fallopian tube among female MMR mutation carriers undergoing prophylactic surgery.     

Lynch综合征相关子宫内膜癌新进展

子宫内膜癌是女性Lynch综合征患者最常见的肠外肿瘤,与散发性子宫内膜癌不同,该病是常染色体显性遗传病,病因及发病机制是错配修复基因(MLH1、MSH2、MSH6及PMS2)的突变或异常表达。患者发病年龄年轻,病理类型多样,包括子宫内膜样癌、透明细胞癌、浆液性癌、未分化癌或癌肉瘤等。由于该病再次发生肿瘤的风险较高,危害大,因此及时治疗Lynch综合征相关的子宫内膜癌是有效预防该类患者再次发生肿瘤的关键。就Lynch综合征相关子宫内膜癌的病因、发病机制、临床病理特征及诊断、治疗和筛查新进展进行综述。     

Current and future approaches to screening for endometrial cancer

Due largely to the rise in obesity and prolonged life expectancy, endometrial cancer (EC) rates have increased by 56% since the early 90s. Women at high risk (Lynch Syndrome) have a 12–47% lifetime risk of developing EC and professional societies recommend annual surveillance using transvaginal ultrasound (TVS) and endometrial biopsy (outpatients hysteroscopy) from the age of 30–35 years with hysterectomy from the age of 40 years. In women at low risk, screening is not currently advocated. The emerging data from Genome Wide Association studies (GWAS) in combination with epidemiological data may refine risk stratification in the future. In addition to screening, preventative approaches such as intrauterine progesterone may help reduce disease burden in those identified at ‘higher risk’.